Jessica L Davis1, Sara O Vargas2, Erin R Rudzinski3, Jessica M López Marti4, Katherine Janeway5, Suzanne Forrest5, Katrina Winsnes6, Navin Pinto7, Sung E Yang1, Mandy VanSandt1, Theonia K Boyd2, Christopher L Corless1, Yajuan J Liu8, Lea F Surrey9, Marian H Harris2, Alanna Church2, Alyaa Al-Ibraheemi2. 1. Department of Pathology, Oregon Health and Science University, Portland, OR, USA. 2. Department of Pathology, Boston Children's Hospital, Boston, MA, USA. 3. Department of Laboratories, Seattle Children's Hospital, Seattle, WA, USA. 4. Department of Pathology, Hospital Nacional de Pediatria Juan P. Garrahan, Buenos Aires, Argentina. 5. Department of Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA. 6. Division of Pediatric Hematology and Oncology, Oregon Health and Science University/Doernbecher Children's Hospital, Portland, OR, USA. 7. Cancer and Blood Disorders Center, Seattle Children's Hospital, University of Washington Medical Center and Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 8. Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA. 9. Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Abstract
AIMS: The classification of paediatric spindle mesenchymal tumours is evolving, and the spectrum of so-called 'infantile fibrosarcoma' has expanded to include tumours with NTRK, BRAF and MET gene fusions. RET-rearranged paediatric spindle cell neoplasms are an emerging group; there is sparse literature on their clinical, pathological and genetic features, and their nosological place in the canon of soft tissue tumours is uncertain. In this study, we report five RET-rearranged paediatric spindle cell tumours with fusion partners MYH10, KIAA1217 and CLIP2. METHODS AND RESULTS: The tumours occurred in the pelvic region, paraspinal region, kidney and subcutaneous tissue of hand and abdomen. The patients' ages ranged from 6 months to 13 years (median 1 year). The tumours were composed of monomorphic spindle cells arranged in a fascicular pattern. Lesional cells had minimally atypical ovoid or tapered nuclei and pale cytoplasm with indistinct borders. Necrosis was not identified. Mitoses numbered three to 12 per 10 high-power field. Cases showed inconsistent and variable expression of S100, CD34 and SMA. Clinical behaviour ranged from small lesions potentially cured by simple resection to large lesions exhibiting metastasis, but responsive to kinase inhibitor therapy. CONCLUSIONS: Our findings help to define RET-rearranged spindle cell tumours. Although it is likely that these tumours comprise part of the morphological and clinical spectrum of infantile fibrosarcoma (IFS), identification of RET gene alteration is important for its unique therapeutic implications.
AIMS: The classification of paediatric spindle mesenchymal tumours is evolving, and the spectrum of so-called 'infantile fibrosarcoma' has expanded to include tumours with NTRK, BRAF and MET gene fusions. RET-rearranged paediatric spindle cell neoplasms are an emerging group; there is sparse literature on their clinical, pathological and genetic features, and their nosological place in the canon of soft tissue tumours is uncertain. In this study, we report five RET-rearranged paediatric spindle cell tumours with fusion partners MYH10, KIAA1217 and CLIP2. METHODS AND RESULTS: The tumours occurred in the pelvic region, paraspinal region, kidney and subcutaneous tissue of hand and abdomen. The patients' ages ranged from 6 months to 13 years (median 1 year). The tumours were composed of monomorphic spindle cells arranged in a fascicular pattern. Lesional cells had minimally atypical ovoid or tapered nuclei and pale cytoplasm with indistinct borders. Necrosis was not identified. Mitoses numbered three to 12 per 10 high-power field. Cases showed inconsistent and variable expression of S100, CD34 and SMA. Clinical behaviour ranged from small lesions potentially cured by simple resection to large lesions exhibiting metastasis, but responsive to kinase inhibitor therapy. CONCLUSIONS: Our findings help to define RET-rearranged spindle cell tumours. Although it is likely that these tumours comprise part of the morphological and clinical spectrum of infantile fibrosarcoma (IFS), identification of RET gene alteration is important for its unique therapeutic implications.
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